The causative factors and modulators of obesity and maturity-onset diabetes will be investigated in experimental animal studies. The early, pre-weaning development of the obese syndrome in genetically obese (ob/ob) mice will be followed. We will identify the ob/ob mice at 8-10 weeks of age and determine whether increased rate of fatty acid synthesis in liver or adipose tissue precedes the increase in fat cell number and size distribution and adipose tissue mass, as well as the subsequent hyperinsulinemia, hyperglycemia and hyperphagia. In other studies, any influence of high fat diets fed dams during gestation and lactation on the development of the obese syndrome in the young will documented. The drug, fenfluramine, will be administered to ob/ob mice to study the metabolic effects (other than anorectic) of this compound in obesity. Effects on insulin resistance, on hyperglycemia and on fatty acid synthesis will be investigated. Comparative studies of related genetic obesities in rodents also will be carried out in order to test the importance of the specific genetic lesion and other genetic factors in the expression of the obese syndromes.